Abstract 6457: Phase I study of STA551 (STA) a tumor-selective CD137 agonist, as monotherapy and in combination with atezolizumab (atezo) using CD8 PET imaging to assess pharmacodynamic effects

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Abstract Background: CD137 is a promising costimulatory receptor for cancer immunotherapy. Several CD137 agonist antibody biologics have been developed, but none show clear promising clinical potential due to severe toxicity. STA, an ATP-dependent switch antibody, is designed to selectively activate CD137 within tumors, and minimize systemic toxicity. We conducted a phase I study of STA alone or the combination of STA and atezo to evaluate tolerability, PK and pharmacodynamics using CD8 PET imaging, in patients with advanced solid tumors. Methods: The Phase 1 study includes dose escalation and CD8 PET cohorts. For the dose escalation cohorts, patients were treated with either STA monotherapy IV q3 weekly or STA in combination with atezo (1200 mg) q3 weekly. For the CD8 PET cohort, patients received STA q3 weekly for two cycles as monotherapy, followed by combination therapy with atezo 1200 mg from cycle 3 onwards. Zr-89 crefmirlimab berdoxam (a minibody targeting CD8, labeled with Zr-89) was used as the tracer of CD8 PET scan. CD8 PET scans were done at baseline, after two STA doses (Cycle 2 Day 9), and after two combination doses (Cycle 4 Day 9). Results: A total of 94 patients were treated in the dose escalation cohorts (41 patients in monotherapy and 41 patients in the combination) and in the CD8 PET cohort (12 patients). The most common treatment related adverse events (≥10%) were AST increased (17.1%), fatigue (14.6%), and ALT increased (12.2%) in mono cohorts; ALT increased (22.6%), AST increased (18.9%), infusion related reaction (IRR) (15.1%), nausea (13.2%), diarrhoea (11.3%) and fatigue (11.3%) in combination and CD8 PET cohorts. No severe adverse events related to Zr-89 crefmirlimab berdoxam were reported. No dose limiting toxicities were observed up to STA 1200 mg alone. The maximum tolerated dose was 450 mg of STA in combination with 1200 mg of atezo administered q3 weekly. The PK analysis showed STA increased in a dose proportional manner. In the CD8 PET cohort, 10 patients were evaluable for efficacy and CD8 PET analyses. One partial response (PR) was observed in a heavily pretreated patient with triple negative breast cancer. Five patients had stable disease. Increased tracer accumulation in tumor lesions was indicated in a subset of patients. Notably, in the patient who achieved a PR, clear increased accumulation was observed in all evaluable lesions. No clear increase in the tracer accumulation was observed in the spleen which has been reported with other systemic CD137 agonists. Conclusions: STA demonstrated a manageable safety profile both as monotherapy and in combination with atezo. CD8 PET analysis suggested STA increased intratumoral CD8+ T cell levels in a subset of patients, with limited effects in normal organs. These findings potentially support the tumor-selective mechanism of action of STA as a CD137 agonist. Citation Format: Udai Banerji, Diogo Silva, Joshua Ting, Zoulikha Zair, Prakash Manoharan, Toshihiko Doi, Shigehiro Koganemaru, Noboru Yamamoto, Takafumi Koyama, Seiichi Ikeda, Yuki Kanai, Michiyasu Inatani, Hitomi Takeshita, Akiko Hashimoto, Yoshitaka Ogita, Yuma Takano, Kei Higashikawa, Fiona Thistlethwaite. Phase I study of STA551 (STA) a tumor-selective CD137 agonist, as monotherapy and in combination with atezolizumab (atezo) using CD8 PET imaging to assess pharmacodynamic effects [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6457.

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